Membrane Phase Separation: An Emerging Biophysical Perspective on Food-Derived Bioactive Peptides

Food-derived bioactive peptides (FDBPs), released from dietary proteins during processing, fermentation, or digestion, exhibit diverse physiological activities that are not fully explained by classical receptor- or enzyme-centered models. Depending on their amino acid composition, physicochemical properties, and assembly state, some FDBPs may interact directly with cellular membranes and modulate lipid organization. Membrane phase separation provides an emerging biophysical framework for interpreting the actions of FDBPs. This review presents a prospective analysis of FDBP-membrane phase interactions, emphasizing available research methods, biological contexts, and structure-activity relationships. In particular, we examine how peptide localization, charged and hydrophobic residues, chemical modification, and multivalent assembly may influence membrane fluidity, thickness, surface charge, and the organization of liquid-ordered and liquid-disordered domains. This perspective has the potential to broaden the mechanistic understanding of FDBPs' bioactivities and to guide the rational design of membrane-targeted functional foods.